2019
PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma
Fons NR, Sundaram RK, Breuer GA, Peng S, McLean RL, Kalathil AN, Schmidt MS, Carvalho DM, Mackay A, Jones C, Carcaboso ÁM, Nazarian J, Berens ME, Brenner C, Bindra RS. PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma. Nature Communications 2019, 10: 3790. PMID: 31439867, PMCID: PMC6706443, DOI: 10.1038/s41467-019-11732-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBrain Stem NeoplasmsCell Line, TumorChildCytokinesDiffuse Intrinsic Pontine GliomaDNA MethylationEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticHumansMiceNicotinamide PhosphoribosyltransferasePonsPrimary Cell CultureProtein Phosphatase 2CSynthetic Lethal MutationsXenograft Model Antitumor AssaysConceptsNicotinic acid phosphoribosyltransferaseSynthetic lethal interactionsNAMPT inhibitorsTumor-specific cell killingProtein phosphataseEpigenetic silencingMutant cellsKey genesCpG islandsLethal interactionsNAD biosynthesisGene expressionInhibitor sensitivityNAD metabolismOncogenic rolePediatric gliomasMutationsModel systemCell killingDriver mutationsPediatric high-grade gliomasMutant tumorsOncogenic driver mutationsNicotinamide phosphoribosyltransferase (NAMPT) inhibitionGenome
2017
Bi‐allelic alterations in DNA repair genes underpin homologous recombination DNA repair defects in breast cancer
Mutter RW, Riaz N, Ng CK, Delsite R, Piscuoglio S, Edelweiss M, Martelotto LG, Sakr RA, King TA, Giri DD, Drobnjak M, Brogi E, Bindra R, Bernheim G, Lim RS, Blecua P, Desrichard A, Higginson D, Towers R, Jiang R, Lee W, Weigelt B, Reis‐Filho J, Powell SN. Bi‐allelic alterations in DNA repair genes underpin homologous recombination DNA repair defects in breast cancer. The Journal Of Pathology 2017, 242: 165-177. PMID: 28299801, PMCID: PMC5516531, DOI: 10.1002/path.4890.Peer-Reviewed Original ResearchConceptsBreast cancerGermline BRCA1/BRCA2 mutationsBRCA1/BRCA2 mutationsPrecision medicine-based approachPrimary breast cancerTumour-specific DNA repair defectsSporadic breast cancerGermline genetic alterationsBi-allelic lossWhole-exome sequencingSpecific mutational signaturesComprehensive genetic assessmentBRCA2 mutationsLarge-scale state transitionsBi-allelic alterationsCancerGenetic alterationsDNA repair defectsMutational signaturesTherapyAlterationsRepair defectsGene expressionGenetic assessmentHR genes
2007
Co-repression of mismatch repair gene expression by hypoxia in cancer cells: Role of the Myc/Max network
Bindra RS, Glazer PM. Co-repression of mismatch repair gene expression by hypoxia in cancer cells: Role of the Myc/Max network. Cancer Letters 2007, 252: 93-103. PMID: 17275176, DOI: 10.1016/j.canlet.2006.12.011.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell Cycle ProteinsCell HypoxiaCell Line, TumorDNA Mismatch RepairDown-RegulationGene Expression Regulation, NeoplasticGenomic InstabilityHumansHypoxia-Inducible Factor 1MutL Protein Homolog 1MutS Homolog 2 ProteinNeoplasmsNuclear ProteinsPromoter Regions, GeneticProto-Oncogene Proteins c-mycRepressor ProteinsConceptsHypoxia-inducible factorHypoxia-induced genetic instabilityGene expressionGenetic instabilityRepair genesStress response pathwaysC-Myc/MaxStress response factorsMismatch repair genesCancer cellsRepair gene expressionMax complexesCoordinated repressionKey genesDNA repairMMR pathwayProximal promoterMicroenvironmental stressMax networkMMR gene expressionDeficient cellsGenesRepressionEssential roleMMR genes
2006
Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia
Bindra RS, Glazer PM. Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia. Oncogene 2006, 26: 2048-2057. PMID: 17001309, DOI: 10.1038/sj.onc.1210001.Peer-Reviewed Original ResearchConceptsDNA repair pathwaysE2F siteRepair pathwaysHypoxia-induced genetic instabilityGenetic instabilityCoordinated transcriptional programRepair genesHypoxic stressRecombinational repair genesDownregulation of Rad51RAD51 gene expressionTranscriptional programsProximal promoterGene expressionNuclear accumulationMechanistic basisDNA mismatch repair genesRAD51BRCA1 promoterGenesPromoterMismatch repair genesBRCA1 geneNew therapeutic strategiesSimilar mechanism
2005
Alterations in DNA Repair Gene Expression under Hypoxia: Elucidating the Mechanisms of Hypoxia‐Induced Genetic Instability
BINDRA RS, SCHAFFER PJ, MENG A, WOO J, MÅSEIDE K, ROTH ME, LIZARDI P, HEDLEY DW, BRISTOW RG, GLAZER PM. Alterations in DNA Repair Gene Expression under Hypoxia: Elucidating the Mechanisms of Hypoxia‐Induced Genetic Instability. Annals Of The New York Academy Of Sciences 2005, 1059: 184-195. PMID: 16382054, DOI: 10.1196/annals.1339.049.Peer-Reviewed Original ResearchConceptsGenetic instabilityHomologous recombinationRAD51 expressionDNA repair gene expressionSuch genetic instabilityPost-hypoxic cellsDNA repair genesRepair gene expressionNumerous cell linesExpression of RAD51HR pathwayHR repairHypoxia-inducible factorGene expressionCell cycleRepair genesNovel mechanismHypoxic stressIndependent mannerPost-hypoxic periodCell linesCancer cellsCritical mediatorGenesExpressionHypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells
Meng AX, Jalali F, Cuddihy A, Chan N, Bindra RS, Glazer PM, Bristow RG. Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells. Radiotherapy And Oncology 2005, 76: 168-176. PMID: 16026872, DOI: 10.1016/j.radonc.2005.06.025.Peer-Reviewed Original ResearchConceptsProstate cancer cellsCell cycle distributionCancer cellsP53 genotypeCycle distributionProtein expressionRNA expressionPoor clinical outcomeInduction of hypoxiaMalignant prostate cell linesAbility of hypoxiaRepair genesProstate cell linesHypoxia-induced apoptosisHR-associated genesDouble-strand break repair genesClinical outcomesDNA double-strand break repair genesProstate cancerGene expressionIntratumoral hypoxiaVEGF expressionBPH-1Tumor cellsObserved genetic instability
2003
Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells
Mihaylova VT, Bindra RS, Yuan J, Campisi D, Narayanan L, Jensen R, Giordano F, Johnson RS, Rockwell S, Glazer PM. Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells. Molecular And Cellular Biology 2003, 23: 3265-3273. PMID: 12697826, PMCID: PMC153206, DOI: 10.1128/mcb.23.9.3265-3273.2003.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenosine TriphosphatasesAnimalsBase Pair MismatchBeta-GalactosidaseCarrier ProteinsCell HypoxiaCells, CulturedDeferoxamineDinucleotide RepeatsDNA RepairDNA Repair EnzymesDNA-Binding ProteinsEnzyme InhibitorsFibroblastsGenes, ReporterHeLa CellsHumansHydroxamic AcidsHypoxia-Inducible Factor 1, alpha SubunitIron Chelating AgentsMethylationMiceMice, TransgenicMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinNeoplasm ProteinsNuclear ProteinsProto-Oncogene ProteinsRNA, MessengerTranscription FactorsConceptsGenetic instabilityMammalian cellsDNA mismatch repair genes MLH1Chromosomal reporter geneHistone deacetylase inhibitor trichostatin AStationary-phase mutagenesisDeacetylase inhibitor trichostatin AInhibitor trichostatin AMismatch repair genes MLH1Treatment of cellsHistone deacetylationStress signalsKey MMR proteinsReporter geneGenes MLH1Gene expressionLow oxygen tensionPMS2 levelsMMR gene expressionTrichostatin AMLH1 mRNAPotential new pathwaysDinucleotide repeatsHeterodimer partnerHypoxia-induced reduction